Novel mutations in the GH gene (GH1) uncover putative splicing regulatory elements.

Mutations affecting exon 3 splicing are the main cause of autosomal dominant Isolated GH Deficiency II (IGHDII) by increasing the level of exon 3-skipped mRNA encoding the functionally inactive dominant-negative 17.5-kDa isoform. The exons and introns of the gene encoding GH (GH1) were screened for the presence of mutations in 103 sporadic isolated GH deficiency cases.

Functional SNPs within the intron 1 of the PROP1 gene contribute to combined growth hormone deficiency (CPHD).

Context: Mutations within the PROP1 gene represent one of the main causes of familial combined pituitary hormone deficiency (CPHD). However, most of the cases are sporadic with an unknown genetic cause.

Objective: The aim of this study was the search for low penetrance variations within and around a conserved regulatory element in the intron 1 of PROP1, contributing to a multifactorial form of the disease in sporadic patients.

Association of HLA class I markers with multiple sclerosis in the Italian and UK population: evidence of two independent protective effects.

Background: The association of HLA A*02 with multiple sclerosis (MS) was recently confirmed by the authors, and it was observed that the combined presence of HLA Cw*05 significantly enhanced (threefold) the protective effect of HLA A*02.

Objectives And Methods: Since A*02-Cw*05 is carried by two HLA extended haplotypes characterised by the B*4402 and B*1801 alleles, respectively, the association analysis was extended to HLA B*44 and B*18 in an Italian sample (1445 MS cases and 973 controls) and these associations were verified in a UK cohort (721 MS cases, 408 controls and 480 family trios).

Results: A strong protective effect, independent of DR15, of the A*02-Cw*05 combination carrying B*44 (OR 0.

HLA-class I markers and multiple sclerosis susceptibility in the Italian population.

Previous studies reported an association with multiple sclerosis (MS) of distinct HLA-class I markers, namely HLA-A*02, HLA-Cw*05 and MOG-142L. In this work, we tested the association with MS of A*02 and Cw*05 in 1273 Italian MS patients and 1075 matched controls, which were previously analyzed for MOG-142, and explored the relationship among these three markers in modulating MS risk. HLA-A*02 conferred a statistically robust MS protection (odds ratio, OR=0.

A recurrent signal peptide mutation in the growth hormone releasing hormone receptor with defective translocation to the cell surface and isolated growth hormone deficiency.

Context: Mutations in the GHRH receptor (GHRHR) have been detected in the familial type-IB isolated GH deficiency (IGHD-IB) inherited as an autosomal recessive disorder and characterized by a low but detectable serum GH level and good response to substitutive GH therapy.

Objective: The aim of our study was the identification of mutations in sporadic patients with a IGHD-IB phenotype.

Subjects And Methods: The GHRHR gene was systematically screened by DHPLC in 134 IGHD patients with no family history of the disorder or declared parental consanguinity.